A comprehensive, systematic and integrated investigation of the antigens present on erythrocytes and other tissues and in body fluids or secretions of man and animals and of their specific antibodies comprising several human blood group systems will be undertaken along two lines of approach. The first and major of these will be a study of the fundamental immunologic characteristics of human blood group isoantigens and antibodies in an attempt to correlate certain physicochemical properties with their serologic characteristics. Emphasis will be placed on the ABO and related blood group systems such as Lewis and I. Experiments will be continued or initiated to differentiate immune anti-A antibodies in the sera of stimulated donors from those in maternal sera in ABO hemolytic disease of the newborn; to study the comparative serology of A antigens and anti-A antibodies using red cells and secretions of animals to analyze anti-A antibodies eluted from erythrocyte stromata in ABO hemolytic disease of the newborn; to develop test systems for the determination of anti-A isohemolysins; to investigate serologically and immunogenically the A substances secreted in saliva; to characterize the blood group A variants; to analyze the O phenotype (Bombay) immunologically; to ascertain the relationship of anti-H antibodies in sheep sera to sheep blood groups; to detect the occurrence of human blood group antigens in addition to the ABH antigens on cells and tissues other than erythrocytes; to study morphologically antibody-mediated hemagglutination by scanning electron microscopy; to examine the basic characteristics of lectins; and to characterize the I blood group system antigens. The second area will be the application of the study of blood groups to human genetics and anthropology. Genetic linkage studies will be carried out by determining the complete hemagglutinogen pattern of family members with inherited defects. The frequency and inheritance of an M antigen variant and the Fy(a-b-) phenotype in Negroes and the phenotype Lu(a-b-) together with its serologic characteristics in a local Caucasian family and anthropologic investigations with emphasis on the frequency of the Di super a antigen will be continued in various Indians and local Polish Americans.